Geburtshilfe Frauenheilkd 2002; 62(3): 234-241
DOI: 10.1055/s-2001-25216
Übersicht

Georg Thieme Verlag Stuttgart · New York

Phytoöstrogene und Brustkrebs - senken Pflanzenöstrogene das Risiko?

Do Phytoestrogens Lower the Risk of Breast Cancer?K. H. Adzersen, I. Gerhard
  • Universitäts-Frauenklinik, Abt. Gynäkologische Endokrinologie und Fertilitätsstörungen, Heidelberg
Further Information

Publication History

Publication Date:
19 April 2002 (online)

Zusammenfassung

Ernährungsfaktoren haben einen signifikanten modulierenden Einfluss auf das Brustkrebsrisiko von Frauen. Epidemiologische Ländervergleichsstudien legen nahe, dass Soja, unraffinierte Korn- und Samenprodukte sowie Gemüse das Brustkrebsrisiko senken könnten. Asiatische Frauen, die sich traditionell und bevorzugt phytoöstrogenreich ernähren, haben eine niedrige Brustkrebsinzidenz und -mortalität. In Migrationsstudien fanden sich niedrige Brustkrebsrisiken bei weiblichen Erste-Generation-Migrantinnen mit einer Kindheit in ihrem asiatischen Heimatland, jedoch schon die zweite Generation verlor mit zunehmendem „westlichen“ Ernährungs- und Lebensstil diesen Schutz.

Fünf von acht Fall-Kontroll-Studien, durchgeführt zwischen 1991 und 1999, zeigten bei prämenopausalen Frauen eine brustkrebsprotektive Wirkung, zwei bei postmenopausalen Frauen und drei Studien keinen Effekt.

Kurzzeitige perinatale oder präpubertäre Phytoöstrogenexposition in experimentellen Rattenmodellen senkte die Brustkrebsrate und die Tumorzahl bei den erwachsenen Tieren um 50 %. Diese ausgeprägte protektive Wirkung war mit einer duktalen Differenzierung des mammären Drüsenbaumes verbunden, woraus eine niedrigere Empfindlichkeit des Brustepithels gegenüber mutagenen Alterationen resultierte, vergleichbar mit dem deutlich brustkrebsprotektiven Effekt einer frühen ersten Schwangerschaft. Niedrige Brustkrebsraten bei asiatischen Frauen könnten somit der Tatsache einer präpubertären Exposition gegenüber Phytoöstrogenen, d. h. einer Soja-Ernährung in der Kindheit, teilweise erklärt werden.

Die vorliegenden Daten legen nahe, dass Phytoöstrogene das Brustkrebsrisiko senken, direkte Belege dafür fehlen aber, da alle bisherigen Kenntnisse auf dem Verzehr phytoöstrogenhaltiger Lebensmittel beruhen. Die derzeitige Datenlage ist aus evidenz-basierter Sicht unzureichend, um eine erhöhte Aufnahme von Phytoöstrogenen zur Brustkrebsprävention zu empfehlen.

Gezielte klinische Interventionsuntersuchungen sind notwendig, um Nutzen und Risiken einer erhöhten Phytoöstrogenaufnahme bei westlichen Frauen abzuschätzen und vermutete krebsprotektive Wirkungen nachzuweisen.

Abstract

Nutritional factors modulate the risk of breast cancer in women. Epidemiologic studies suggest that diets high in soy, unrefined grain and vegetables may lower the risk of breast cancer. Asian women with a traditional diet high in plant estrogens have a low incidence of and mortality from breast cancer. Migration studies show a low risk of breast cancer in first-generation female migrants with an Asian home country; however, in the second generation with an increasingly Western diet this protection is lost.

Of eight case-control studies performed between 1991 and 1999, five suggest a protective effect for premenopausal women, two a protective effect for premenopausal and postmenopausal women, and three no effect.

Short-term perinatal or prepubertal phytoestrogen exposure in rat models reduced the incidence of chemically-induced breast cancer and the number of tumors in adulthood by 50 %. This pronounced protective effect is associated with ductal differentiation of the mammary gland tree resulting in a lowered susceptibility of the breast epithelium to mutagenic alterations, comparable to the protective effect of an early first pregnancy. The low risk of breast cancer in Asian females might thus be due to prepubertal exposure to phytoestrogens in a soy-rich diet. The data suggest that phytoestrogens may lower the risk of breast cancer, but there is no direct evidence in humans because current information is based on the consumption of phytoestrogens in food. The existing data do not justify a recommendation for increased phytoestrogen intake to prevent breast cancer. Focused clinical intervention studies are necessary to assess benefits and risks of phytoestrogen intake in Western women to prove a putative cancer protective effect.

Literatur

  • 1 Adlercreutz H, Fotsis T, Heikkinen R, Dwyer J T, Woods M, Goldin B R, Gorbach S L. Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer.  Lancet. 1982;  8311 1295-1299
  • 2 Adlercreutz H, Fotsis T, Bannwart C, Wahala K, Makela T, Brunow G, Hase T. Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets.  J Steroid Biochem. 1986;  25(5 B) 791-797
  • 3 Adlercreutz H, Bannwart C, Wahala K. et al . Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens.  J Steroid Biochem Mol Biol. 1993;  44 147-153
  • 4 Adlercreutz H. Phytoestrogens: epidemiology and a possible role in cancer protection.  Environ Health Perspect. 1995;  103 (Suppl 7) 103-112
  • 5 Adlercreutz H, Mousavi Y, Clark J, Hockerstedt K, Hamalainen E, Wahala K, Makela T, Hase T. Dietary phytoestrogens and cancer: in vitro and in vivo studies.  J Steroid Biochem Mol Biol. 1992;  41 331-337
  • 6 Adlercreutz H, Yamada T, Wahala K, Watanabe S. Maternal and neonatal phytoestrogens in Japanese women during birth.  Am J Obstet Gynecol. 1999;  180 737-743
  • 7 Akiyama T, Ishida J, Nakagawa S. et al . Genistein, a specific inhibitor of tyrosinase-specific protein kinases.  J Biol Chem. 1987;  262 5592-5595
  • 8 Arai Y, Uehara M, Sato Y, Kimira M, Eboshida A, Adlercreutz H, Watanabe S. Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake.  J Epidemiol. 2000;  10 127-135
  • 9 Barnes S. Effect of genistein on in vitro and in vivo models of cancer.  J Nutr. 1995;  125 (3 Suppl) 777S-783S
  • 10 Boice J D, Preston D, Davis F G, Monson R R. Frequent chest X-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts.  Radiat Res. 1991;  125 214-222
  • 11 Bradlow H L, Telang N T, Sepkovic D W, Osborne M P. Phytochemicals as modulators of cancer risk.  Adv Exp Med Biol. 1999;  472 207-221
  • 12 Braun M M, Ahlbom A, Floderus B, Brinton L A, Hoover R N. Effect of twinship on incidence of cancer of the testis, breast, and other sites (Sweden).  Cancer Causes Control. 1995;  6 519-524
  • 13 Brown N M, Wang J, Cotroneo M S, Zhao Y X, Lamartiniere C A. Prepubertal genistein treatment modulates TGF-alpha, EGF and EGF-receptor mRNAs and proteins in the rat mammary gland.  Mol Cell Endocrinol. 1998;  144 149-165
  • 14 Brzezinski A, Debi A. Phytoestrogens: the “natural” selective estrogen receptor modulators?.  Eur J Obstet Gynecol Reprod Biol. 1999;  85 47-51
  • 15 Cassidy A. Physiological effects of phyto-oestrogens in relation to cancer and other human health risks.  Proc Nutr Soc. 1996;  55 399-417
  • 16 Cassidy A. Potential tissue selectivity of dietary phytoestrogens and estrogens.  Curr Opin Lipidol. 1999;  10 47-52
  • 17 Cassidy A, Bingham S, Setchell K D. Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women.  Am J Clin Nutr. 1994;  60 333-340
  • 18 Chen S. Aromatase and breast cancer.  Front Biosci. 1998;  3 922-933
  • 19 Chen H, Tritton T R, Kenny N, Absher M, Chiu J F. Tamoxifen induces TGF-beta 1 activity and apoptosis of human MCF-7 breast cancer cells in vitro.  J Cell Biochem. 1996;  61 9-17
  • 20 Chie W C, Hsieh C, Newcomb P A, Longnecker M P, Mittendorf R, Greenberg E R, Clapp R W, Burke K P, Titus-Ernstoff L, Trentham-Dietz A, MacMahon B. Age at any full-term pregnancy and breast cancer risk.  Am J Epidemiol. 2000;  151 715-722
  • 21 Choi Y H, Zhang L, Lee W H, Park K Y. Genistein-induced G2/M arrest is associated with the inhibition of cyclin B1 and the induction of p21 in human breast carcinoma cells.  Int J Oncol. 1998;  13 391-396
  • 22 Colditz G A. Fat, estrogens, and the time frame for prevention of breast cancer.  Epidemiology. 1995;  6 209-211
  • 23 Colditz G A, Frazier A L. Models of breast cancer show that risk is set by events of early life: prevention efforts must shift focus.  Cancer Epidemiol Biomarkers Prev. 1995;  4 567-571
  • 24 Constantinou A, Huberman E. Genistein as an inducer of tumor cell differentiation: possible mechanisms of action.  Proc Soc Exp Biol Med. 1995;  208 109-115
  • 25 Ekbom A, Trichopoulos D, Adami H O, Hsieh C C, Lan S J. Evidence of prenatal influences on breast cancer risk.  Lancet. 1992;  340 1015-1018
  • 26 Fattman C L, An B, Sussman L, Dou Q P. p53-independent dephosphorylation and cleavage of retinoblastoma protein during tamoxifen-induced apoptosis in human breast carcinoma cells.  Cancer Lett. 1998;  130 103-113
  • 27 Foth D, Cline J M, Romer T. Effect of isoflavones on mammary gland and endometrium of postmenopausal macaques.  Zentralbl Gynäkol. 2000;  122 96-102
  • 28 Fotsis T, Pepper M, Adlercreutz H, Fleischmann G, Hase T, Montesano R, Schweigerer L. Genistein, a dietary-derived inhibitor of in vitro angiogenesis.  Proc Natl Acad Sci USA. 1993;  90 2690-2694
  • 29 Fotsis T, Zhang Y, Pepper M S, Adlercreutz H, Montesano R, Nawroth P P, Schweigerer L. The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth.  Nature. 1994;  368 237-239
  • 30 Hawrylewicz E J, Zapata J J, Blair W H. Soy and experimental cancer: animal studies.  J Nutr. 1995;  125 (3 Suppl) 698S-708S
  • 31 Henderson B E, Bernstein L. The international variation in breast cancer rates: an epidemiological assessment.  Breast Cancer Res Treat. 1991;  18 (Suppl 1) S11-17
  • 32 Hilakivi-Clarke L, Clarke R, Onojafe I, Raygada M, Cho E, Lippman M. A maternal diet high in n-6 polyunsaturated fats alters mammary gland development, puberty onset, and breast cancer risk among female rat offspring.  Proc Natl Acad Sci USA. 1997;  94 9372-9377
  • 33 Hirose K, Tajima K, Hamajima N, Inoue M, Takezaki T, Kuroishi T, Yoshida M, Tokudome S. A large-scale, hospital-based case-control study of risk factors of breast cancer according to menopausal status.  Jpn J Cancer Res. 1995;  86 146-154
  • 34 Holmes M D, Hunter D J, Colditz G A, Stampfer M J, Hankinson S E, Speizer F E, Rosner B, Willett W C. Association of dietary intake of fat and fatty acids with risk of breast cancer.  JAMA. 1999;  281 914-920
  • 35 Hunter D J, Willett W C. Diet, body size, and breast cancer.  Epidemiol Rev. 1993;  15 110-132
  • 36 Ingram D, Sanders K, Kolybaba M, Lopez D. Case-control study of phyto-oestrogens and breast cancer.  Lancet. 1997;  350 990-994
  • 37 Jefcoate C R, Liehr J G, Santen R J, Sutter T R, Yager J D, Yue W, Santner S J, Tekmal R, Demers L, Pauley R, Naftolin F, Mor G, Berstein L. Tissue-specific synthesis and oxidative metabolism of estrogens.  J Natl Cancer Inst Monogr. 2000;  2000 95-112
  • 38 Key T J, Sharp G B, Appleby P N, Beral V, Goodman M T, Soda M, Mabuchi K. Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan.  Br J Cancer. 1999;  81 1248-1256
  • 39 Key T J, Fraser G E, Thorogood M, Appleby P N, Beral V, Reeves G, Burr M L, Chang-Claude J, Frentzel-Beyme R, Kuzma J W, Mann J, McPherson K. Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies.  Am J Clin Nutr. 1999;  70 (3 Suppl) 516S-524S
  • 40 Kim H, Muller W J. The role of the epidermal growth factor receptor family in mammary tumorigenesis and metastasis.  Exp Cell Res. 1999;  253 78-87
  • 41 Kim H, Peterson T G, Barnes S. Mechanisms of action of the soy isoflavone genistein: emerging role for its effects via transforming growth factor beta signaling pathways.  Am J Clin Nutr. 1998;  68 (6 Suppl) 1418S-1425S
  • 42 Knekt P, Adlercreutz H, Rissanen H, Aromaa A, Teppo L, Heliovaara M. Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer?.  Br J Cancer. 2000;  82 1107-1110
  • 43 Knight D C, Eden J A. A review of the clinical effects of phytoestrogens.  Obstet Gynecol. 1996;  87 897-904
  • 44 Kuiper G G, Lemmen J G, Carlsson B, Corton J C, Safe S H, van der Saag P T, van der Burg B, Gustafsson J A. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta.  Endocrinology. 1998;  139 4252-4263
  • 45 Lamartiniere C A, Moore J B, Brown N M, Thompson R, Hardin M J, Barnes S. Genistein suppresses mammary cancer in rats.  Carcinogenesis. 1995;  16 2833-2840
  • 46 Lamartiniere C A, Murrill W B, Manzolillo P A, Zhang J X, Barnes S, Zhang X, Wei H, Brown N M. Genistein alters the ontogeny of mammary gland development and protects against chemically-induced mammary cancer in rats.  Proc Soc Exp Biol Med. 1998;  217 358-364
  • 47 Lamartiniere C A. (Discussion 1708 S - 9 S. ) Protection against breast cancer with genistein: a component of soy.  Am J Clin Nutr. 2000;  71 (6 Suppl) 1705S-1707S
  • 48 Lawrence D A. Transforming growth factor-beta: a general review.  Eur Cytokine Netw. 1996;  7 363-374
  • 49 Lee H P, Gourley L, Duffy S W, Esteve J, Lee J, Day N E. Dietary effects on breast-cancer risk in Singapore.  Lancet. 1991;  337 1197-1200
  • 50 Li Y, Bhuiyan M, Sarkar F H. Induction of apoptosis and inhibition of c-erbB-2 in MDA-MB-435 cells by genistein.  Int J Oncol. 1999;  15 525-533
  • 51 Liggins J, Grimwood R, Bingham S A. Extraction and quantification of lignan phytoestrogens in food and human samples.  Anal Biochem. 2000;  287 102-109
  • 52 Lu L J, Anderson K E, Grady J J, Nagamani M. Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction.  Cancer Epidemiol Biomarkers Prev. 1996;  5 63-70
  • 53 Lu L J, Anderson K E, Grady J J, Kohen F, Nagamani M. Decreased ovarian hormones during a soya diet: implications for breast cancer prevention.  Cancer Res. 2000;  60 4112-4121
  • 54 MacMahon B, Cole P, Brown J. Etiology of human breast cancer: a review.  J Natl Cancer Inst. 1973;  50 21-42
  • 55 McMichael-Phillips D F, Harding C, Morton M, Roberts S A, Howell A, Potten C S, Bundred N J. Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast.  Am J Clin Nutr. 1998;  68 (6 Suppl) 1431S-1435S
  • 56 Messina M J, Persky V, Setchell K D, Barnes S. Soy intake and cancer risk: a review of the in vitro and in vivo data.  Nutr Cancer. 1994;  21 113-131
  • 57 Michels K B, Trichopoulos D, Robins J M, Rosner B A, Manson J E, Hunter D J, Colditz G A, Hankinson S E, Speizer F E, Willett W C. Birthweight as a risk factor for breast cancer.  Lancet. 1996;  348 1542-1546
  • 58 Mousavi Y, Adlercreutz H. Genistein is an effective stimulator of sex hormone-binding globulin production in hepatocarcinoma human liver cancer cells and suppresses proliferation of these cells in culture.  Steroids. 1993;  58 301-304
  • 59 Murkies A L, Wilcox G, Davis S R. Clinical review 92: Phytoestrogens.  J Clin Endocrinol Metab. 1998;  83 297-303
  • 60 Murrill W B, Brown N M, Zhang J X, Manzolillo P A, Barnes S, Lamartiniere C A. Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats.  Carcinogenesis. 1996;  17 1451-1457
  • 61 Musey P I, Adlercreutz H, Gould K G, Collins D C, Fotsis T, Bannwart C, Makela T, Wahala K, Brunow G, Hase T. Effect of diet on lignans and isoflavonoid phytoestrogens in chimpanzees.  Life Sci. 1995;  57 655-664
  • 62 Nagata C, Takatsuka N, Inaba S, Kawakami N, Shimizu H. Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women.  J Natl Cancer Inst. 1998;  90 1830-1835
  • 63 Parkin D M, Pisani P, Ferlay J. Global cancer statistics.  CA Cancer J Clin. 1999;  49 33-64
  • 64 Peterson G, Barnes S. Genistein inhibition of the growth of human breast cancer cells: independence from estrogen receptors and the multi-drug resistance gene.  Biochem Biophys Res Commun. 1991;  179 661-667
  • 65 Phipps W R, Martini M C, Lampe J W, Slavin J L, Kurzer M S. Effect of flax seed ingestion on the menstrual cycle.  J Clin Endocrinol Metab. 1993;  77 1215-1219
  • 66 Pike M, Krailo M, Casagrande J, Hoel D. “Hormonal” risk factors, “breast tissue age” and the age-incidence of breast cancer.  Nature. 1983;  303 767-770
  • 67 Pike M C, Spicer D V, Dahmoush L, Press M F. Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk.  Epidemiol Rev. 1993;  15 17-35
  • 68 Potischman N, Troisi R. In-utero and early life exposures in relation to risk of breast cancer.  Cancer Causes Control. 1999;  10 561-573
  • 69 Reinli K, Block G. Phytoestrogen content of foods - a compendium of literature values.  Nutr Cancer. 1996;  26 123-148
  • 70 Rosner B, Colditz G, Willett W. Reproductive factors in a prospective study of breast cancer: the Nurses' Health Study.  Am J Epidemiol. 1995;  139 819-835
  • 71 Rowland I R, Wiseman H, Sanders T A, Adlercreutz H, Bowey E A. Interindividual variation in metabolism of soy isoflavones and lignans: influence of habitual diet on equol production by the gut microflora.  Nutr Cancer. 2000;  36 27-32
  • 72 Rowland I, Wiseman H, Sanders T, Adlercreutz H, Bowey E. Metabolism of oestrogens and phytoestrogens: role of the gut microflora.  Biochem Soc Trans. 1999;  27 304-308
  • 73 Russo J, Russo I H. Influence of differentiation and cell kinetics on the susceptibility of the rat mammary gland to carcinogenesis.  Cancer Res. 1980;  40 2677-2687
  • 74 Russo J, Gusterson B, Rogers A E, Russo I CH, Wellings S R, van Zwieten M J. Biology of disease: comparative study of human and rat mammary tumorigenesis.  Lab Invest. 1990;  62 244-278
  • 75 Russo I H, Koszalka M, Russo J. Human chorionic gonadotropin and rat mammary cancer prevention.  J Natl Cancer Inst. 1990;  82 1286-1289
  • 76 Russo I, Russo J. Physiological basis of breast cancer prevention.  Eur J Cancer Prev. 1993;  2 (Suppl) 101-111
  • 77 Russo J, Hu Y F, Yang X, Russo I H. Developmental, cellular, and molecular basis of human breast cancer.  J Natl Cancer Inst Monogr. 2000;  27 17-37
  • 78 Setchell K D, Cassidy A. Dietary isoflavones: biological effects and relevance to human health.  J Nutr. 1999;  129 758S-767S
  • 79 Setchell K D, Zimmer-Nechemias L, Cai J, Heubi J E. Isoflavone content of infant formulas and the metabolic fate of these phytoestrogens in early life.  Am J Clin Nutr. 1998;  68 (6 Suppl) 1453S-1461S
  • 80 Setchell K D, Zimmer-Nechemias L, Cai J, Heubi J E. Exposure of infants to phyto-oestrogens from soy-based infant formula.  Lancet. 1997;  350 23-27
  • 81 Steinmetz K A, Potter J D. Vegetables, fruit, and cancer. II. Mechanisms.  Cancer Causes Control. 1991;  2 427-442
  • 82 Tokunaga M, Land C E, Tokuoka S, Nishimori I, Soda M, Akiba S. Incidence of female breast cancer among atomic bomb survivors, 1950 - 1985.  Radiat Res. 1994;  138 209-223
  • 83 Tou J C, Thompson L U. Exposure to flaxseed or its lignan component during different developmental stages influences rat mammary gland structures.  Carcinogenesis. 1999;  20 1831-1835
  • 84 Ursin G, Bernstein L, Pike M C. Breast cancer.  Cancer Surv. 1994;  19 - 20 241-264
  • 85 Wang T T, Sathyamoorthy N, Phang J M. Molecular effects of genistein on estrogen receptor mediated pathways.  Carcinogenesis. 1996;  17 271-275
  • 86 Wilcox G, Wahlqvist M L, Burger H G, Medley G. Oestrogenic effects of plant foods in postmenopausal women.  BMJ. 1990;  301 905-906
  • 87 Wohlfahrt J, Melbye M. Age at any birth is associated with breast cancer risk.  Epidemiology. 2001;  12 68-73
  • 88 World Cancer Research Fund/American Institute for Cancer Research (Washington D. C. ). Food, Nutrition and the Prevention of Cancer: a Global Perspective. Menasha, Wisconsin; Banta Book Group 1997
  • 89 Wu A H, Ziegler R G, Nomura A M, West D W, Kolonel L N, Horn-Ross P L, Hoover R N, Pike M C. Soy intake and risk of breast cancer in Asians and Asian Americans.  Am J Clin Nutr. 1998;  68 (6 Suppl) 1437S-1443S
  • 90 Xu X, Duncan A M, Merz B E, Kurzer M S. Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women.  Cancer Epidemiol Biomarkers Prev. 1998;  7 1101-1108
  • 91 Yu W, Heim K, Qian M, Simmons-Menchaca M, Sanders B G, Kline K. Evidence for role of transforming growth factor-beta in RRR-alpha-tocopheryl succinate-induced apoptosis of human MDA-MB-435 breast cancer cells.  Nutr Cancer. 1997;  27 267-278
  • 92 Yuan J M, Wang Q S, Ross R K, Henderson B E, Yu M C. Diet and breast cancer in Shanghai and Tianjin, China.  Br J Cancer. 1995;  71 1353-1358
  • 93 Zheng W, Dai Q, Custer L J, Shu X O, Wen W Q, Jin F, Franke A A. Urinary excretion of isoflavonoids and the risk of breast cancer.  Cancer Epidemiol Biomarkers Prev. 1999;  8 35-40

Dr. med. Karl-Heinrich Adzersen

Universitäts-Frauenklinik, Abt. 4.2 Gynäkologische Endokrinologie und Fertilitätsstörungen

Voßstraße 9

69115 Heidelberg

Email: karl-heinrich_adzersen@med.uni-heidelberg.de

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